No relationship between frontal alpha asymmetry and depressive disorders in a multiverse analysis of five studies

  1. Aleksandra Kołodziej  Is a corresponding author
  2. Mikołaj Magnuski
  3. Anastasia Ruban
  4. Aneta Brzezicka
  1. University of Social Sciences and Humanities, Poland
  2. Cedars-Sinai Medical Center Department of Neurosurgery, United States
9 figures, 13 tables and 1 additional file

Figures

Diagram describing the five studies included in this article (Studies I, II, III, IV, and V).

(A) Number of participants for each study and group (see Table 12 for details). (B) Stacked histograms showing the distribution of BDI or PHQ-9 scores in each study and each group. (C) Channel montage. Frontal channels used in cluster-based analyses are marked with gray dots. Channels used in channel-pairs analysis are marked with teal dots (F3–F4, F7–F8, and corresponding channels in the EGI montage). (D) Rest period length and scheme.

Analysis variants used (described in detail in Variants of statistical analysis section).

(A) Schematic depiction of given statistical contrast: group comparisons (left) vs regression (right). (B) Specification of each contrast against depression scores. Left panel shows a schematic range of depression scores for each contrast: diagnosed vs healthy controls (DvsHC) and sub-clinical vs healthy controls (SvsHC). Right panel shows the range of depression scores for data included in each linear contrast: regression on diagnosed subjects (DReg) uses only subjects with clinical diagnosis, while regression on all subjects (allReg) uses all subject groups. The color legend for the subject groups is presented below these figures. (C) Analysis space: AVG – channel level, average reference; CSD – channel level, current source density; SRC – source level, DICS beamforming. (D) Schematic depiction of analysis method: selected channel pairs versus all frontal channels with cluster-based correction for multiple comparisons.

Selected results for channel-pairs level analyses, depressed vs healthy controls (DvsHC) contrast.

Panels A and B show 2 of 3 significant channel pair results: average referenced F3–F4 channel pair for Studies I (A) and V (B). The remaining panels (C and D) show other channel pair analysis variants: specifically those that differ by exactly one parameter (underlined text) from the result presented in the panel A. Horizontal lines represent averages for each group, and shaded areas show standard error of the mean.

Figure 4 with 4 supplements
Selected results of cluster-based analyses: topographies of DvsHC contrast effects in a reference by study matrix.

More positive (red) t values indicate more right-sided (less left-sided) alpha asymmetry for diagnosed participants. More negative (blue) t values indicate more right-sided (less left-sided) FAA for healthy controls. Channels that are part of a cluster are marked with white dots.

Figure 4—figure supplement 1
Results of cluster-based analyses for allReg contrast (regression on all subjects).

Topographies of effects are presented in a reference by study matrix. Color bar on the right presents color coding for the t values: more positive (red)/negative (blue) relationship between FAA and BDI. Channels that are part of a cluster are marked with white dots.

Figure 4—figure supplement 2
Results of cluster-based analyses for DReg contrast (regression on diagnosed subjects).

Topographies of effects are presented in a reference by study matrix. Color bar on the right presents color coding for the t values: more positive (red)/negative (blue) relationship between FAA and BDI. Channels that are part of a cluster are marked with white dots.

Figure 4—figure supplement 3
Results of cluster-based analyses for SvsHC (comparison between subclinical and healthy controls) contrast.

Topographies of different contrast effects in a reference by study matrix. More positive (red) t values indicate more right-sided (less left-sided) alpha asymmetry for subclinical participants. More negative (blue) t values indicate more right-sided (less left-sided) FAA for healthy controls. Channels that are part of a cluster are marked with white dots.

Figure 4—figure supplement 4
An example of a more detailed visualization of asymmetry effects: group-level averages for DvsHC, Study V, AVG from F.

First row shows topography of average alpha power for both groups; second row shows topography of average alpha asymmetry for both groups.

Selected results of cluster-based analyses showing the influence of statistical control for confounding variables like age, gender (Studies I and V), and education (Study V).

(A) The logic of the topographical plots is the same as in Figure 4. (B) Swarmplots corresponding to studies in panel A showing the between-group difference in the selected confounding variables. Detailed results for analyses taking into account confounding variables can be found in Table 4.

Figure 6 with 4 supplements
Selected results of cluster-based analyses on standardized data.

Heatmaps in the upper part of each panel represent regression t values for channel by frequency search space. More positive/negative t values indicate higher/lower power with higher BDI. Clusters are indicated in the heatmaps with white outline. In each panel we present two topographies below the heatmap: showing average effect for lower and higher frequency ranges determined by the positions of the clusters. Channels that are part of a cluster are marked with white dots in the topographical plots.

Figure 6—figure supplement 1
Results of cluster-based analyses on standardized data for allReg contrast (linear regression between FAA and BDI on all subjects together).

Heatmaps in the upper part of each panel represent regression t values for channel by frequency search space. More positive/negative t values indicate higher/lower power with higher BDI. Clusters are indicated in the heatmaps with white outline. In each panel we present two topographies below the heatmap: showing average effect for 9–10 Hz and 11.5–12.5 Hz range respectively. Channels that are part of a cluster are marked with white dots in the topographical plots.

Figure 6—figure supplement 2
Results of cluster-based analyses on standardized data for DReg contrast (linear regression between FAA and BDI restricted to the non-diagnosed subjects).

Heatmaps in the upper part of each panel represent regression t values for channel by frequency search space. More positive/negative t values indicate higher/lower power with higher BDI. Clusters are indicated in the heatmaps with white outline. In each panel we present two topographies below the heatmap: showing average effect for 9–10 Hz and 11.5–12.5 Hz range respectively. Channels that are part of a cluster are marked with white dots in the topographical plots.

Figure 6—figure supplement 3
Results of cluster-based analyses on standardized data for DvsHC contrast (comparison between diagnosed and healthy controls).

Heatmaps in the upper part of each panel represent t values for channel by frequency search space. More positive (red) t values indicate higher power in given channel and frequency for diagnosed participants. More negative (blue) t values indicate higher power in given channel and frequency for healthy controls. Clusters are indicated in the heatmaps with white outline. In each panel we present two topographies below the heatmap: showing average effect for 9–10 Hz and 11.5–12.5 Hz range respectively. Channels that are part of a cluster are marked with white dots in the topographical plots.

Figure 6—figure supplement 4
Results of cluster-based analyses on standardized data for SvsHC contrast (comparison between subclinical and healthy controls).

Heatmaps in the upper part of each panel represent t values for channel by frequency search space. More positive (red) t values indicate higher power in given channel and frequency for diagnosed participants. More negative (blue) t values indicate higher power in given channel and frequency for healthy controls. Clusters are indicated in the heatmaps with white outline. In each panel we present two topographies below the heatmap: showing average effect for 9–10 Hz and 11.5–12.5 Hz range respectively. Channels that are part of a cluster are marked with white dots in the topographical plots.

Figure 7 with 4 supplements
Selected results of source level analyses showing spatial t value maps for respective contrasts.

Cluster limits are marked with white outlines, and corresponding cluster p-values are shown below each panel. Color bar at the bottom presents color coding for the t values.

Figure 7—figure supplement 1
Results of source level analyses for allReg contrast (linear regression between FAA and BDI on all subjects) showing spatial t value maps for regression analyses.

Cluster limits are marked with white outlines, and corresponding cluster p-values are shown below each panel. Color bar at the bottom presents color coding for the t values: more positive (red)/negative (blue) relationship between FAA and BDI.

Figure 7—figure supplement 2
Results of source level analyses for DReg contrast (linear regression between FAA and BDI restricted to diagnosed subjects) showing spatial t value maps for regression analyses.

Cluster limits are marked with white outlines, and corresponding cluster p-values are shown below each panel. Color bar at the bottom presents color coding for the t values: more positive (red)/negative (blue) relationship between FAA and BDI. Linear regression restricted to diagnosed subjects; NA: no cluster with p<0.05 is present.

Figure 7—figure supplement 3
Results of source level analyses for DvsHC contrast (comparison between diagnosed and healthy controls) showing spatial t value maps for regression analyses.

Cluster limits are marked with white outlines, corresponding cluster p-values are shown below each panel. More positive (red) t values indicate more right-sided (less left-sided) alpha asymmetry for diagnosed participants. More negative (blue) t values indicate more right-sided (less left-sided) FAA for healthy controls.

Figure 7—figure supplement 4
Results of source level analyses for SvsHC contrast (comparison between subclinical and healthy controls) showing spatial t value maps for regression analyses.

Cluster limits are marked with white outlines, corresponding cluster p-values are shown below each panel. More positive (red) t values indicate more right-sided (less left-sided) alpha asymmetry for subclinical participants. More negative (blue) t values indicate more right-sided (less left-sided) FAA for healthy controls. NA: no cluster with p<0.05 is present.

Figure 8 with 2 supplements
Results for channel pair analyses where studies including identical group contrasts (A) and linear contrasts (B) are combined.

Each row corresponds to one analysis on a single channel pair. The contrasts, studies, and channel pairs are labeled on the y axis. The black dots correspond to observed effect sizes in Cohen’s d/Pearson’s r, while the black lines indicate 95% confidence intervals for the effect size estimated using bias-corrected accelerated bootstrapping. The magenta/purple shapes represent bootstrap distributions and the white numbers printed on the distributions are Bayes factors for the null hypothesis (BF01). BF01 of 4 indicates that the data are four times more likely under the null than the alternative hypothesis. BF01 between 3 and 10 are considered moderate evidence for the null hypothesis.

Figure 8—figure supplement 1
Results for channel pair analyses with control for confounds where studies including identical group contrasts (A) and linear contrasts (B) are combined.

Each row corresponds to one analysis on a single channel pair. The contrasts, studies, and channel pairs are labeled on the y axis. The black dots correspond to observed effect sizes in Cohen’s d/Pearson’s r, while the black lines indicate 95% confidence intervals for the effect size estimated using bias-corrected accelerated bootstrapping. The magenta/purple shapes represent bootstrap distributions and the white numbers printed on the distributions are Bayes factors for the null hypothesis (BF01). BF01 of 4 indicates that the data are four times more likely under the null than the alternative hypothesis. BF01 between 3 and 10 are considered moderate evidence for the null hypothesis.

Figure 8—figure supplement 2
Results for channel pair gender × contrast interaction analyses on aggregated data with control for confounds.

In group contrasts (A) the interaction term is female * diagnosed; in linear contrasts (B) it is female * depression score. Each row corresponds to one analysis on a single channel pair. The contrasts, studies, and channel pairs are labeled on the y axis. The black dots correspond to observed effect sizes in Pearson’s r, while the black lines indicate 95% confidence intervals for the effect size estimated using bias-corrected accelerated bootstrapping. The magenta/purple shapes represent bootstrap distributions and the white numbers printed on the distributions are Bayes factors for the null hypothesis (BF01). BF01 of 4 indicates that the data are four times more likely under the null than the alternative hypothesis. BF01 between 3 and 10 are considered moderate evidence for the null hypothesis.

Figure 9 with 2 supplements
Selected results for aggregated source space analyses showing spatial t value maps for respective contrasts.

Cluster limits are marked with white outlines, and corresponding cluster p-values are shown below each panel. Color bar at the bottom presents color coding for the t values.

Figure 9—figure supplement 1
Selected results for aggregated source space analyses showing spatial t value maps for respective contrasts.

Cluster limits are marked with white outlines, and corresponding cluster p-values are shown below each panel. Color bar at the bottom presents color coding for the t values.

Figure 9—figure supplement 2
Results for interaction analyses (gender × contrast) for aggregated studies in source space.

In group contrasts (DvsHC and SvsHC) the interaction term is female * diagnosed; in linear contrasts (DReg, allReg) it is female * depression score. Cluster limits are marked with white outlines, and corresponding cluster p-values are shown below each panel. Color bar at the bottom presents color coding for the t values.

Tables

Table 1
Results for all channel-pair analyses.

Each row represents two channel-pair results for a given contrast, study, and space combination; uncorrected for multiple comparisons. Electrode placement for each study is shown in Figure 1C. (N: number of participants included in given contrast; ES: effect size; Cohen’s d for group comparison and Pearson’s r for regression; CI: bootstrap 95% confidence interval for the effect size).

No.ContrastStudySpaceNSelected electrodes without correction
Pair 1 (F3–F4)Pair 2 (F7–F8)
tpESCItpESCI
1DvsHCIavg29 vs 22−2.0730.043−0.573[−1.135,–0.024]−0.3650.717−0.101[−0.644, 0.465]
2DvsHCIcsd29 vs 220.1320.8960.038[−0.550, 0.608]0.5530.5830.153[−0.415, 0.689]
3DvsHCIIIavg27 vs 210.9040.3710.247[−0.316, 0.689]−0.5360.595−0.145[−0.760, 0.452]
4DvsHCIIIcsd27 vs 210.8490.4010.226[−0.307, 0.721]−0.1290.898−0.035[−0.590, 0.536]
5DvsHCIVavg22 vs 720.4500.6540.094[−0.310, 0.510]0.2770.7830.059[−0.413, 0.463]
6DvsHCIVcsd22 vs 720.7670.4490.212[−0.287, 0.771]−1.3960.172−0.345[−0.808, 0.167]
7DvsHCVavg24 vs 292.8230.0070.743[0.218, 1.255]1.9270.0610.501[−0.023, 0.998]
8DvsHCVcsd24 vs 290.7480.4580.208[−0.380, 0.775]−0.7270.471−0.202[−0.766, 0.370]
9SvsHCIIavg23 vs 280.2010.8410.056[−0.502, 0.614]−0.6620.511−0.179[−0.780, 0.381]
10SvsHCIIcsd23 vs 281.1440.2580.318[−0.221, 0.827]−0.1990.843−0.054[−0.611, 0.508]
11SvsHCIIIavg33 vs 21−0.8520.398−0.209[−0.640, 0.306]−1.3280.190−0.332[−0.804, 0.216]
12SvsHCIIIcsd33 vs 21−1.1810.244−0.280[−0.730, 0.219]−1.0940.280−0.302[−0.798, 0.219]
13SvsHCIVavg21 vs 721.3590.1840.346[−0.198, 0.816]1.2470.2190.254[−0.138, 0.646]
14SvsHCIVcsd21 vs 720.5580.5810.147[−0.393, 0.655]0.1410.8890.035[−0.388, 0.605]
15allRegIavg54−1.1380.260−0.156[−0.397, 0.088]−0.1800.858−0.025[−0.394, 0.258]
16allRegIcsd54−0.5400.591−0.075[−0.309, 0.167]0.0770.9390.011[−0.335, 0.280]
17allRegIIIavg910.5450.5870.058[−0.105, 0.263]−0.7810.437−0.083[−0.271, 0.101]
18allRegIIIcsd910.2090.8350.022[−0.169, 0.207]0.4220.6740.045[−0.168, 0.225]
19allRegIVavg1171.1380.2580.106[−0.076, 0.264]0.6750.5010.063[−0.111, 0.212]
20allRegIVcsd1171.3070.1940.121[−0.096, 0.312]−1.0240.308−0.095[−0.265, 0.093]
21allRegVavg532.4890.0160.329[0.106, 0.517]1.4630.1500.201[−0.023, 0.409]
22allRegVcsd530.8570.3950.119[−0.127, 0.361]−0.2200.827−0.031[−0.262, 0.210]
23DRegIavg290.9800.3360.185[−0.212, 0.531]0.3200.7510.061[−0.470, 0.522]
24DRegIcsd29−1.3030.204−0.243[−0.540, 0.091]−0.5040.618−0.097[−0.501, 0.337]
25DRegIIIavg270.2780.7840.055[−0.268, 0.426]0.0550.9570.011[−0.273, 0.238]
26DRegIIIcsd270.4070.6880.081[−0.254, 0.413]1.3470.1900.260[−0.047, 0.498]
27DRegIVavg221.7540.0950.365[0.012, 0.643]−0.1140.910−0.026[−0.459, 0.427]
28DRegIVcsd221.9380.0670.398[−0.043, 0.632]−0.4150.683−0.092[−0.519, 0.351]
29DRegVavg241.4970.1490.304[0.045, 0.563]−0.3670.717−0.078[−0.444, 0.285]
30DRegVcsd240.7890.4380.166[−0.264, 0.501]0.6350.5320.134[−0.320, 0.615]
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 2
Results for all channel-pair analyses corrected for confounds.

Each row represents two channel-pair results for a given contrast, study, and space combination; uncorrected for multiple comparisons. Electrode placement for each study is shown in Figure 1C. (N: number of participants included in given contrast; ES: effect size; Cohen’s d for group comparison and Pearson’s r for regression; CI: bootstrap 95% confidence interval for the effect size).

No.ContrastStudySpaceNSelected electrodes corrected for confounds
Pair 1 (F3–F4)Pair 2 (F7–F8)
tpESCItpESCI
1DvsHCIavg29 vs 22−2.6790.010−0.789[−1.413,–0.218]−0.7820.438−0.230[−0.691, 0.288]
2DvsHCIcsd29 vs 220.2690.7890.079[−0.501, 0.681]0.3050.7620.090[−0.404, 0.622]
3DvsHCIIIavg27 vs 210.2040.8390.064[−0.642, 0.684]−1.1610.252−0.366[−0.994, 0.310]
4DvsHCIIIcsd27 vs 21−0.1620.872−0.051[−0.691, 0.547]−0.7030.486−0.221[−0.998, 0.558]
5DvsHCIVavg22 vs 710.3100.7570.077[−0.338, 0.504]0.0850.9330.021[−0.412, 0.450]
6DvsHCIVcsd22 vs 710.9780.3310.244[−0.250, 0.816]−1.4840.141−0.370[−0.842, 0.135]
7DvsHCVavg24 vs 291.8620.0690.540[0.033, 1.044]1.8170.0750.527[−0.008, 1.101]
8DvsHCVcsd24 vs 290.5180.6070.150[−0.415, 0.742]−0.7220.474−0.209[−0.689, 0.235]
9SvsHCIIavg23 vs 280.3510.7280.105[−0.444, 0.746]−0.6540.516−0.196[−0.883, 0.450]
10SvsHCIIcsd23 vs 281.2930.2030.387[−0.152, 0.943]0.0350.9720.010[−0.653, 0.532]
11SvsHCIIIavg33 vs 21−1.1690.248−0.350[−0.946, 0.285]−1.7680.084−0.529[−1.071, 0.029]
12SvsHCIIIcsd33 vs 21−1.3820.173−0.414[−1.086, 0.160]−1.1970.237−0.358[−0.997, 0.212]
13SvsHCIVavg21 vs 711.0580.2930.269[−0.232, 0.776]0.4660.6420.118[−0.293, 0.515]
14SvsHCIVcsd21 vs 710.7390.4620.188[−0.302, 0.649]−0.2630.793−0.067[−0.524, 0.483]
15allRegIavg54−1.3520.182−0.188[−0.440, 0.078]−0.3490.728−0.049[−0.369, 0.240]
16allRegIcsd54−0.4310.668−0.061[−0.313, 0.187]−0.0190.985−0.003[−0.335, 0.304]
17allRegIIIavg910.2330.8160.025[−0.156, 0.263]−1.1700.245−0.127[−0.313, 0.092]
18allRegIIIcsd91−0.0050.996−0.001[−0.190, 0.204]−0.0600.953−0.007[−0.238, 0.224]
19allRegIVavg1160.9040.3680.085[−0.088, 0.237]0.3550.7230.034[−0.139, 0.197]
20allRegIVcsd1161.4610.1470.137[−0.064, 0.316]−1.3000.196−0.122[−0.296, 0.059]
21allRegVavg531.6850.0990.236[−0.014, 0.449]1.5440.1290.218[−0.034, 0.433]
22allRegVcsd530.7690.4460.110[−0.148, 0.339]−0.0580.954−0.008[−0.214, 0.185]
23DRegIavg290.7670.4500.152[−0.324, 0.503]0.2650.7930.053[−0.452, 0.564]
24DRegIcsd29−1.2730.215−0.247[−0.588, 0.156]−0.5060.617−0.101[−0.504, 0.437]
25DRegIIIavg27−0.0540.958−0.012[−0.434, 0.485]−0.0790.937−0.018[−0.425, 0.346]
26DRegIIIcsd270.0550.9570.012[−0.407, 0.408]1.3750.1840.294[−0.096, 0.614]
27DRegIVavg221.9790.0630.423[−0.001, 0.719]−0.0620.951−0.015[−0.409, 0.473]
28DRegIVcsd221.7610.0950.383[0.004, 0.674]−0.2690.791−0.063[−0.538, 0.418]
29DRegVavg240.9260.3660.208[−0.209, 0.565]−0.7070.488−0.160[−0.571, 0.278]
30DRegVcsd240.7230.4780.164[−0.345, 0.554]0.2980.7690.068[−0.569, 0.735]
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 3
Results for cluster-based permutation test on frontal asymmetry space.

Each row represents cluster-based results for a given contrast, study, and space combination (N: number of participants included in given contrast; min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster size: number of channels participating in the cluster; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis).

No.ContrastStudySpaceNCluster-based permutation test on frontal asymmetry space
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHCIavg29 vs 22−2.1100.0233130.069
2DvsHCIcsd29 vs 22−0.7201.98300NANA
3DvsHCIIIavg27 vs 21−1.1721.05800NANA
4DvsHCIIIcsd27 vs 21−1.2581.87500NANA
5DvsHCIVavg22 vs 72−0.7512.0691110.345
6DvsHCIVcsd22 vs 72−1.6001.14200NANA
7DvsHCVavg24 vs 29−1.2602.8236250.026
8DvsHCVcsd24 vs 29−2.9011.4252210.156
9SvsHCIIavg23 vs 28−2.5810.2011110.164z
10SvsHCIIcsd23 vs 28−0.8551.25400NANA
11SvsHCIIIavg33 vs 21−1.4101.02100NANA
12SvsHCIIIcsd33 vs 21−2.3152.1012210.227
13SvsHCIVavg21 vs 72−1.3562.7602120.052
14SvsHCIVcsd21 vs 72−1.1931.29600NANA
15allRegIavg54−1.5190.02200NANA
16allRegIcsd54−0.7271.05200NANA
17allRegIIIavg91−1.2070.90600NANA
18allRegIIIcsd91−1.2902.2101110.287
19allRegIVavg117−1.8072.1531110.202
20allRegIVcsd117−1.1731.35300NANA
21allRegVavg53−1.0012.4893130.077
22allRegVcsd53−3.2911.5522210.187
23DRegIavg29−0.1591.55200NANA
24DRegIcsd29−1.3030.48700NANA
25DRegIIIavg27−2.0410.97600NANA
26DRegIIIcsd27−1.4201.66200NANA
27DRegIVavg22−1.1551.75400NANA
28DRegIVcsd22−0.4151.93800NANA
29DRegVavg24−1.4821.49700NANA
30DRegVcsd24−2.2541.5541110.555
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 4
Results for cluster-based permutation test on frontal asymmetry space corrected for confounds.

Each row represents cluster-based results for a given contrast, study and space combination (N: number of participants included in given contrast; min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster size: number of channels participating in the cluster; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis).

No.ContrastStudySpaceNCluster-based permutation test on frontal asymmetry space corrected for confounds
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHCIavg29 vs 22−2.679−0.1495150.023
2DvsHCIcsd29 vs 22−1.0201.59100NANA
3DvsHCIIIavg27 vs 21−1.5061.36100NANA
4DvsHCIIIcsd27 vs 21−1.3101.37800NANA
5DvsHCIVavg22 vs 71−0.8141.81200NANA
6DvsHCIVcsd22 vs 71−1.8120.97800NANA
7DvsHCVavg24 vs 29−1.6182.3413310.327
8DvsHCVcsd24 vs 29−3.0170.7382210.205
9SvsHCIIavg23 vs 28−2.6220.3511110.177
10SvsHCIIcsd23 vs 28−0.8381.74200NANA
11SvsHCIIIavg33 vs 21−1.7681.21800NANA
12SvsHCIIIcsd33 vs 21−2.0901.8991110.358
13SvsHCIVavg21 vs 71−1.5841.49000NANA
14SvsHCIVcsd21 vs 71−1.4000.73900NANA
15allRegIavg54−1.7260.03900NANA
16allRegIcsd54−0.8160.98700NANA
17allRegIIIavg91−1.2310.72200NANA
18allRegIIIcsd91−1.5402.1191110.335
19allRegIVavg116−1.8041.85200NANA
20allRegIVcsd116−1.3001.46100NANA
21allRegVavg53−1.2862.3501110.324
22allRegVcsd53−3.5410.8322210.173
23DRegIavg29−0.2441.51600NANA
24DRegIcsd29−1.2910.56500NANA
25DRegIIIavg27−1.7000.85200NANA
26DRegIIIcsd27−1.3111.57400NANA
27DRegIVavg22−1.1732.7281110.121
28DRegIVcsd22−0.2692.2351110.260
29DRegVavg24−1.5930.92600NANA
30DRegVcsd24−2.0752.5862210.376
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 5
Results for all cluster-based analyses on standardized data.

Each row represents cluster-based results for given contrast, study, and space (N: number of participants included in given contrast). Results for cluster-based permutation test on frontal asymmetry space (min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster size: number of channels by frequency points participating in the cluster; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis).

No.ContrastStudySpaceNCluster-based analyses on standardized data
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHCIavg29 vs 22−1.4531.43400NANA
2DvsHCIcsd29 vs 22−2.2271.8793220.718
3DvsHCIIIavg27 vs 21−1.9992.3262120.468
4DvsHCIIIcsd27 vs 21−2.9173.882233160.063
5DvsHCIVavg22 vs 72−4.2563.0531292660.007
6DvsHCIVcsd22 vs 72−3.1802.58222760.259
7DvsHCVavg24 vs 29−2.5162.267213150.223
8DvsHCVcsd24 vs 29−2.7032.42010630.723
9SvsHCIIavg23 vs 28−1.6852.1851110.774
10SvsHCIIcsd23 vs 28−2.0591.7141110.941
11SvsHCIIIavg33 vs 21−1.9061.94600NANA
12SvsHCIIIcsd33 vs 21−2.2843.0917430.577
13SvsHCIVavg21 vs 72−2.3192.51919550.306
14SvsHCIVcsd21 vs 72−2.9503.130254110.092
15allRegIavg54−1.2951.45000NANA
16allRegIcsd54−2.0821.8991111.000
17allRegIIIavg91−1.8141.94900NANA
18allRegIIIcsd91−2.6262.54714460.692
19allRegIVavg117−3.4062.701754400.079
20allRegIVcsd117−2.6442.918325130.179
21allRegVavg53−2.7522.321226130.477
22allRegVcsd53−3.7332.02315650.891
23DRegIavg29−2.0111.93600NANA
24DRegIcsd29−2.7212.0938531.000
25DRegIIIavg27−4.1673.824892530.025
26DRegIIIcsd27−3.5253.285344170.105
27DRegIVavg22−1.8022.2131110.888
28DRegIVcsd22−2.2192.89012490.316
29DRegVavg24−2.9264.155587180.354
30DRegVcsd24−3.5513.084469140.387
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 6
Results for all cluster-based analyses on standardized data corrected for confounds.

Each row represents cluster-based results for given contrast, study, and space (N: number of participants included in given contrast). Results for cluster-based permutation test on frontal asymmetry space (min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster size: number of channels by frequency points participating in the cluster; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis).

No.ContrastStudySpaceNCluster-based analyses on standardized data corrected for confounds
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHCIavg29 vs 22−1.7661.71600NANA
2DvsHCIcsd29 vs 22−2.0071.61400NANA
3DvsHCIIIavg27 vs 21−1.3871.89600NANA
4DvsHCIIIcsd27 vs 21−3.3453.05417460.567
5DvsHCIVavg22 vs 71−4.2953.3041432720.006
6DvsHCIVcsd22 vs 71−3.0952.854335120.179
7DvsHCVavg24 vs 29−1.9821.97600NANA
8DvsHCVcsd24 vs 29−2.0262.79810470.772
9SvsHCIIavg23 vs 28−1.5111.84100NANA
10SvsHCIIcsd23 vs 28−2.0591.8761111.000
11SvsHCIIIavg33 vs 21−2.9642.422225100.374
12SvsHCIIIcsd33 vs 21−2.4243.56212440.865
13SvsHCIVavg21 vs 71−2.6672.858343310.113
14SvsHCIVcsd21 vs 71−2.3893.317233100.273
15allRegIavg54−1.4041.61400NANA
16allRegIcsd54−1.7522.1554221.000
17allRegIIIavg91−2.1191.9635150.612
18allRegIIIcsd91−2.5582.825253170.112
19allRegIVavg116−3.4143.009924540.038
20allRegIVcsd116−2.5713.112326110.216
21allRegVavg53−1.9422.0571111.000
22allRegVcsd53−3.0052.36211550.945
23DRegIavg29−1.9021.99000NANA
24DRegIcsd29−2.5832.0889540.955
25DRegIIIavg27−3.9383.530704360.073
26DRegIIIcsd27−3.1984.098397210.035
27DRegIVavg22−2.2132.6624220.659
28DRegIVcsd22−3.0563.114164100.265
29DRegVavg24−3.2004.246847270.266
30DRegVcsd24−3.5333.378787360.092
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 7
Results for all source level analyses.

Each row represents source level results for given contrast, study, and space (N: number of participants included in given contrast). Results for cluster-based permutation test on frontal asymmetry source space (min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis).

No.ContrastStudyNSource level analysis
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHCI29 vs 22−1.9062.4042120.489
2DvsHCIII27 vs 21−2.5571.158294140.267
3DvsHCIV22 vs 72−3.9211.15132023160.010
4DvsHCV24 vs 29−2.6120.943241240.207
5SvsHCII23 vs 28−0.9091.32100NANA
6SvsHCIII34 vs 21−1.8091.34100NANA
7SvsHCIV21 vs 72−2.3390.679111110.340
8allRegI54−2.3191.549201200.367
9allRegIII92−2.2320.290212200.343
10allRegIV117−2.2201.211101100.466
11allRegV53−2.6441.20115360.574
12DRegI29−2.2921.150412220.328
13DRegIII27−2.624−0.375263180.335
14DRegIV22−1.2162.06400NANA
15DRegV24−2.0681.75800NANA
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects.

Table 8
Results for all source level analyses corrected for confounds.

Each row represents source level results for given contrast, study, and space (N: number of participants included in given contrast) Results for cluster-based permutation test on frontal asymmetry source space (min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis).

No.ContrastStudyNSource level analysis corrected for confounds
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHCI29 vs 22−1.4162.0571110.708
2DvsHCIII27 vs 21−2.1611.7043220.555
3DvsHCIV22 vs 71−3.6851.06636523460.011
4DvsHCV24 vs 29−2.6300.287643460.231
5SvsHCII23 vs 28−0.8141.91100NANA
6SvsHCIII34 vs 21−1.7701.52600NANA
7SvsHCIV21 vs 71−2.732−0.083581580.192
8allRegI54−1.8461.14300NANA
9allRegIII92−2.1950.698151150.391
10allRegIV116−2.3130.910444190.375
11allRegV53−2.9010.317794360.264
12DRegI29−2.1641.010152110.428
13DRegIII27−2.9910.175663630.186
14DRegIV22−1.3971.81800NANA
15DRegV24−2.8931.784221220.352
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; nonDReg – linear regression for only the non-diagnosed subjects.

Table 9
Results for analyses on data aggregated across studies: tests on frontal asymmetry on selected channel pairs.

Each row represents a given contrast × reference × control for confounds combination. N: number of participants included in given contrast, control for confounds: whether the FAA data was residualized with respect to confounding variables (age, gender and education); ES: effect size, measured as Cohen’s d for DvsHC and SvsHC contrasts and Spearman’s r for Dreg and allReg contrasts; CI: bootstrap confidence interval for the effect size; BF01: Bayes Factor for the null hypothesis.

No.ContrastSpaceNControl for confoundsAggregated channel pair analyses
Pair 1 (F3–F4)Pair 2 (F7–F8)
ESCIBF01ESCIBF01
1DvsHCavg102 vs 1440.147[−0.111, 0.396]3.8310.098[−0.161, 0.338]5.405
2DvsHCavg102 vs 143+−0.011[−0.264, 0.244]7.042−0.006[−0.266, 0.240]7.042
3DvsHCcsd102 vs 1440.188[−0.069, 0.449]2.597−0.100[−0.354, 0.164]5.319
4DvsHCcsd102 vs 143+0.103[−0.159, 0.362]5.236−0.164[−0.417, 0.108]3.300
5SvsHCavg77 vs 1210.065[−0.236, 0.359]5.780−0.025[−0.320, 0.240]6.250
6SvsHCavg77 vs 120+0.024[−0.269, 0.315]6.211−0.144[−0.447, 0.140]4.016
7SvsHCcsd77 vs 1210.053[−0.223, 0.355]5.952−0.108[−0.372, 0.179]4.878
8SvsHCcsd77 vs 120+0.053[−0.222, 0.350]5.952−0.110[−0.389, 0.179]4.831
9DRegavg1020.188[0.006, 0.354]1.3870.007[−0.186, 0.188]8.065
10DRegavg102+0.175[−0.018, 0.348]1.742−0.029[−0.211, 0.155]7.752
11DRegcsd1020.099[−0.072, 0.260]4.9750.065[−0.136, 0.252]6.579
12DRegcsd102+0.051[−0.131, 0.216]7.0920.048[−0.157, 0.255]7.194
13allRegavg3150.085[−0.017, 0.184]4.6510.029[−0.080, 0.126]12.5
14allRegavg314+0.041[−0.063, 0.143]10.870.001[−0.120, 0.104]14.085
15allRegcsd3150.059[−0.054, 0.166]8.333−0.026[−0.141, 0.082]12.821
16allRegcsd314+0.055[−0.056, 0.168]8.772−0.048[−0.158, 0.059]9.901
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects; avg – average reference; csd – current source density.

Table 10
Results for analyses on data aggregated across studies, cluster-based permutation tests on frontal asymmetry in the source space.

Each row represents the result for given contrast × control for confounds combination. N: number of participants included in given contrast, control for confounds: whether the FAA data was residualized with respect to confounding variables (age, gender and education), min t, max t: lowest and highest t value in the search space, respectively; n significant points: total number of significant points in the search space before cluster-based correction; n clusters: number of clusters found in given analysis; largest cluster p: p-value for the largest cluster, NA means that no cluster was found in given analysis.

No.ContrastNControl for confoundsAggregated source level analyses
Min tMax tn significant pointsn clustersLargest cluster sizeLargest cluster p
1DvsHC102 vs 144−2.7190.95617851000.077
2DvsHC102 vs 143+−2.8460.90821151160.066
3SvsHC77 vs 121−1.831−0.1100NANA
4SvsHC77 vs 120+−1.8710.18200NANA
5DReg102−2.3871.376313250.328
6DReg102+−3.0951.3541123680.155
7allReg315−3.0440.41117461600.067
8allReg314+−3.1070.28223561950.054
  1. DvsHC – diagnosed and healthy controls; SvsHC – sub-clinical and healthy controls; allReg – linear regression for all subjects together; DReg – linear regression for only diagnosed subjects.

Table 11
Number of significant results compatible with the traditional FAA effect partitioned into analyses and contrasts.

If one or more such results have been found for a given cell, then the p-value for the binomial test is also shown.

Number of significant results congruent with the FAA effect
Channel pairs N = 120Cluster correction N = 60Source space N = 30
DvsHC2/32, p=0.481/16, p=0.562/8, p=0.057
SvsHC0/240/120/6
DReg0/320/160/8
allReg0/320/160/8
Table 12
Descriptive statistics for each study presented in the article (N – number of participants, M – mean score, SD – standard deviation, BDI-I and BDI-II – Beck Depression Inventory I and II, PHQ-9 – Patient Health Questionnaire-9).
Study I (N=51)
DiagnosedHealthy Controls, BDI-I ≤ 5SubclinicalUnclassified
N2922--
AgeM = 27.66, SD = 7.13M = 23.68, SD = 2.83--
19 - 47 range20 - 33 range--
Gender9 male, 20 female11 male, 11 female--
BDI-I scoreM = 20.93, SD = 8.21M = 2.00, SD = 1.48--
Study II (N=76)
Undiagnosed (N=76)
DiagnosedHealthy Controls, BDI-I ≤ 5Subclinical, BDI-I ≥ 10Unclassified, 5 < BDI-I < 10
N-282523
Age-M = 25.32, SD = 6.46M = 24.44, SD = 5.08M = 25.22, SD = 6.78
-18 - 43 range19 - 38 range18 - 40 range
Gender-8 males, 20 females4 males, 21 females9 males, 14 females
BDI-I score-M = 2.29, SD = 1.72M = 17.56, SD = 8.13M = 7.91, SD = 1.16
Study III (N=91)
DiagnosedUndiagnosed (N=64)
Healthy Controls, BDI-II ≤ 5Subclinical, BDI-II ≥ 10Unclassified, 5 < BDI-II < 10
N2721349
AgeM = 27.19, SD = 7.23M = 24.29, SD = 4.99M = 25.06, SD = 6.58M = 26.78, SD = 8.74
19 - 42 range19 - 41 range18 - 44 range22 - 49 range
Gender6 males, 21 females7 males, 14 females10 males, 24 females2 males, 7 females
BDI-II scoreM = 34.26, SD = 9.18M = 2.24, SD = 1.70M = 24.06, SD = 10.08M = 6.78, SD = 0.97
Study IV (N=117)
DiagnosedUndiagnosed (N=95)
Healthy Controls, BDI-II ≤ 5Subclinical, BDI-II ≥ 10Unclassified, 5 < BDI-II < 10
N2272212
(12 past MDD, 10 present MDD)
AgeM = 18.91, SD = 1.34M = 19.00, SD = 1.23M = 18.43, SD = 0.81M = 18.00
18 - 24 range18 - 23 range18 - 21 rangeages 18, 18
Gender8 males, 14 females33 males, 39 females3 males, 18 females1 males, 1 females
BDI-II scoreM = 21.82, SD = 5.70M = 1.60, SD = 1.48M = 22.95, SD = 4.25M = 6.50, SD = 0.71
Study V (N=53)
DiagnosedHealthy Controls, PHQ-9 ≤ 5SubclinicalUnclassified
N2429--
AgeM = 30.88, SD = 10.37M = 31.45, SD = 9.15--
16 - 52 range19 - 52 range--
Gender13 males, 11 females11 males, 13 females--
PHQ-9 scoreM = 18.33, SD = 3.50M = 2.66, SD = 1.80--
Table 13
Summary of the contrasts (DvsHC – diagnosed vs healthy controls; SvsHC – sub-clinical vs healthy controls; allReg – linear regression between FAA and depression questionnaire score for all subjects together; DReg – linear regression only for the diagnosed subjects) and confounds (age, gender, and education) used in each study.
STUDY
IIIIIIIVV
Contrast type
DvsHC++++
SvsHC+++
allReg++++
DReg++++
Control for confounds
gender+++++
age+++++
education+++

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  1. Aleksandra Kołodziej
  2. Mikołaj Magnuski
  3. Anastasia Ruban
  4. Aneta Brzezicka
(2021)
No relationship between frontal alpha asymmetry and depressive disorders in a multiverse analysis of five studies
eLife 10:e60595.
https://doi.org/10.7554/eLife.60595